Forsøksdyr: Studies on B cell tolerance and the interactions between B cells and T cells in celiac disease.

Godkjenningsdato 04.09.2018

Central in the pathogenesis of celiac disease are T cells reactive to gluten peptides and autoreactive B cells producing antibodies to the enzyme TG2. Using transgenic mice, the objectives of the experiments described in this application are to 1: Further understand the development and function of autoreactive TG2-specific B cells, 2: Characterize novel HLA-DQ2 knock in and 3. new gluten-specific T-cell receptor transgenic mice, 4: understand the mechanisms of collaboration between TG2-specific B cells and gluten-specific T cells. This project will be crucial for the understanding of the formation of autoantibodies in patients with celiac disease.
The distress of most animals will be minimal. Mice are expected to develop mild pain for a short amount of time due to intravenous, intraperitoneal and intramuscular injections, oral gavages and the withdrawal of blood (minimum of 6 days between blood samples). The injected antigens will not cause any discomfort to the animals and volumes are kept small to minimize distress. A minor group of mice will experience moderate distress. These include mice that will receive a bone marrow transfer and mice that will be treated with poly:IC and are expected to develop diarrhea and considerable weightloss (together 67 / 967 mice in total). We have kept the number of animals per group at a minimum that is necessary to obtain statistically significant differences and the application includes pilot experiments aimed at reducing the number of mice.